STAT4 and T-bet control follicular helper T cell development in viral infections

Jason S. Weinstein, Brian J. Laidlaw, Yisi Lu, Jessica K. Wang, Vincent P. Schulz, Ningcheng Li, Edward I. Herman, Susan M. Kaech, Patrick G. Gallagher, Joe Craft

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-γ. IL-21 and IFN-γ are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response. T-bet is important for Tfh cell production of IFN-γ, but not IL-21, and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection, is required for expression of T-bet and Bcl6 and for IFN-γ and IL-21. These data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required alongside STAT4 to coordinate Tfh cell IL-21 and IFN-γ production and for promotion of the GC response after acute viral challenge.

Original languageEnglish (US)
Pages (from-to)337-355
Number of pages19
JournalJournal of Experimental Medicine
Volume215
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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